Abstract
Purpose
Bevacizumab is a human monoclonal IgG1 antibody that blocks the action of vascular endothelial growth factor (VEGF). The purpose of this study was to determine the level of VEGF and pigment epithelium-derived factor (PEDF) in eyes with proliferative diabetic retinopathy (PDR) before and after an intravitreal injection of bevacizumab.
Methods
Eleven eyes of ten patients were studied. Patients were included if they had neovascular glaucoma, rubeosis of the iris with PDR, or aggressive PDR. Samples of aqueous humor were collected just before the injection of bevacizumab and the vitrectomy. The concentrations of VEGF and PEDF in the aqueous humor were measured by enzyme-linked immunosorbent assay, and the effects of bevacizumab on PDR were evaluated.
Results
The free VEGF concentration before the injection was 676.5 ± 186.7 pg/ml (mean ± SEM, n = 11). Seven days later, it was significantly reduced to 7.1 ± 7.1 pg/ml (P < 0.005, n = 9). The PEDF concentration before the injection was 2.32 ± 0.49 μg/ml (n = 11), and 7 days later, it was 3.23 ± 0.76 μg/ml (P = 0.33). During the vitrectomy, patients had less intraoperative bleeding when the neovascular tissues were cut.
Conclusions
An intravitreal injection of bevacizumab significantly decreased the free VEGF in the aqueous humor by 7 days, indicating that the clinical effects of bevacizumab appear rapidly. However, intravitreal bevacizumab did not affect the level of intraocular PEDF.
Similar content being viewed by others
References
Adamis AP, Miller JW, Bernal MT, et al. Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy. Am J Ophthalmol 1994;118:445–450.
Aiello LP, Avery RL, Arrigg PG, et al. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med 1994;331:1480–1487.
Malecaze F, Clamens S, Simorre-Pinatel V, et al. Detection of vascular endothelial growth factor messenger RNA and vascular endothelial growth factor-like activity in proliferative diabetic retinopathy. Arch Ophthalmol 1994;112:1476–1482.
Adamis AP, Shima DT, Tolentino MJ, et al. Inhibition of vascular endothelial growth factor prevents retinal ischemia associated iris neovascularization in a nonhuman primate. Arch Ophthalmol 1996;114:66–71.
Aiello LP, Pierce EA, Foley ED, et al. Suppression of retinal neovascularization in vivo by inhibition of vascular endothelial growth factor (VEGF) using soluble VEGF-receptor chimeric proteins. Proc Natl Acad Sci U S A 1995;92:10457–10461.
Rosenfeld PJ, Moshfeghi AA, Puliafito CA. Optical coherence tomography findings after an intravitreal injection of bevacizumab (Avastin) for neovascular age-related macular degeneration. Ophthalmic Surg Lasers Imaging 2005;36:331–335.
Avery RL, Pieramici DJ, Rabena MD, Castellarin AA, Nasir MA, Giust MJ. Intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration. Ophthalmology 2006;113:363–372.
Rosenfeld PJ, Fung AE, Puliafito CA. Optical coherence tomography findings after an intravitreal injection of bevacizumab (Avastin) for macular edema from central retinal vein occlusion. Ophthalmic Surg Lasers Imaging 2005;36:336–339.
Avery RL. Regression of retinal and iris neovascularization after intravitreal bevacizumab (Avastin). Retina 2006;26:352–354.
Jorge R, Costa RA, Calucci D, Cintra LP, Scott IU. Intravitreal bevacizumab (Avastin) for persistent new vessels in diabetic retinopathy (IBEPE study). Retina 2006;26:1006–1013.
Avery RL, Pearlman J, Pieramici DJ, et al. Intravitreal bevacizumab (Avastin) in the treatment of proliferative diabetic retinopathy. Ophthalmology 2006;113:1695–1705.
Haritoglou C, Kook D, Neubauer A, et al. Intravitreal bevacizumab (Avastin) therapy for persistent diffuse diabetic macular edema. Retina 2006;26:999–1005.
Kahook MY, Schuman JS, Noecker RJ. Intravitreal bevacizumab in a patient with neovascular glaucoma, Ophthalmic Surg Lasers Imaging 2006;37:144–146.
Davidorf FH, Mouser JG, Derick RJ. Rapid improvement of rubeosis iridis from a single bevacizumab (Avastin) injection, Retina 2006;26:354–356.
Yazdani S, Hendi K, Pakravan M. Intravitreal bevacizumab (Avastin) injection for neovascular glaucoma. J Glaucoma 2007;16:437–439.
Tombran-Tink J, Johnson LV. Neuronal differentiation of retinoblastoma cells induced by medium conditioned by human RPE cells. Invest Ophthalmol Vis Sci 1989;30:1700–1707.
Dawson DW, Volpert OV, Gillis P, et al. Pigment epithelium-derived factor: a potent inhibitor of angiogenesis. Science 1999;285:245–248.
Stellmach V, Crawford SE, Zhou W, Bouck N. Prevention of ischemia-induced retinopathy by the natural ocular antiangiogenic agent pigment epithelium-derived factor. Proc Nat Acad Soc U S A 2001;98:2593–2597.
Spranger J, Osterhoff M, Reimann M, et al. Loss of antiangiogenic pigment epithelium-derived factor in patients with angiogenic eye diseases. Diabetes 2001;50:2641–2645.
Ogata N, Tombran-Tink J, Nishikawa M, et al. Pigment epithelium-derived factor in the vitreous is low in diabetic retinopathy and high in rhegmatogenous retinal detachment. Am J Ophthalmol 2001;132:378–382.
Ogata N, Nishikawa M, Nishimura T, Mitsuma Y, Matsumura M. Unbalanced vitreous levels of pigment epithelium-derived factor and vascular endothelial growth factor in diabetic retinopathy. Am J Ophthalmol 2002;134:348–353.
Mori K, Duh E, Gehlbach P, et al. Pigment epithelium-derived factor inhibits retinal and choroidal neovascularization. J Cell Physiol 2001;188:253–263.
Liu H, Ren JG, Cooper WL, Hawkins CE, Cowan MR, Tonq PY. Identification of the antivasopermeability effect of pigment epithelium-derived factor and its active site. Proc Natl Acad Sci U S A 2004;101:6605–6610.
Ohno-Matsui K, Yoshida T, Uetama T, Mochizuki M, Morita I. Vascular endothelial growth factor up-regulates pigment epithelium-derived factor expression via VEGFR-1 in human retinal pigment epithelial cells. Biochem Biophys Res Commun 2003;303:962–967.
Mordenti J, Thomsen K, Licko V, et al. Intraocular pharmacokinetics and safety of a humanized monoclonal antibody in rabbits after intravitreal administration of a solution or a PLGA microsphere formulation. Toxicol Sci 1999;52:101–106.
Shahar J, Avery RL, Heilweil G, et al. Electrophysiologic and retinal penetration studies following intravitreal injection of bevacizumab (Avastin). Retina 2006;26:262–269.
Heiduschka P, Fietz H, Hofmeister S, et al. Tubingen Bevacizumab Study Group. Penetration of bevacizumab through the retina after intravitreal injection in the monkey. Invest Ophthalmol Vis Sci 2007;48:2814–2823.
Bakri SJ, Snyder MR, Reid JM, Pulido JS, Singh RJ. Pharmacokinetics of intravitreal bevacizumab (Avastin). Ophthalmology 2007;114:855–859.
Sawada O, Kawamura H, Kakinoki M, Sawada T, Ohji M. Vascular endothelial growth factor in aqueous humor before and after intravitreal injection of bevacizumab in eyes with diabetic retinopathy. Arch Ophthalmol 2007;125:1363–1366.
Miyamoto K, Khosrof S, Bursell SE, et al. Vascular endothelial growth factor (VEGF)-induced retinal vascular permeability is mediated by intercellular adhesion molecule-1 (ICAM-1). Am J Pathol 2000;156:1733–1739.
Matsuoka M, Ogata N, Minamino K, Matsumura M. Leukostasis and pigment epithelium-derived factor in rat models of diabetic retinopathy. Mol Vis 2007;13:1058–1065.
Zhang SX, Wang JJ, Gao G, Parke K, Ma JX. Pigment epithelium-derived factor downregulates vascular endothelial growth factor (VEGF) expression and inhibits VEGF-VEGF receptor 2 binding in diabetic retinopathy. J Mol Endocrinol 2006;37:1–12.
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Matsuyama, K., Ogata, N., Jo, N. et al. Levels of vascular endothelial growth factor and pigment epithelium-derived factor in eyes before and after intravitreal injection of bevacizumab. Jpn J Ophthalmol 53, 243–248 (2009). https://doi.org/10.1007/s10384-008-0645-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10384-008-0645-4